title: Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential.
abstract: Sox2(+) adult mouse pituitary cells can self-renew and terminally differentiate in vitro, but their physiological role in vivo and possible contribution to oncogenesis remain largely unknown. Using genetic lineage tracing, we show here that the Sox2(+) cell compartment of both the embryonic and adult pituitary contains stem/progenitor cells that are able to differentiate into all hormone-producing lineages and contribute to organ homeostasis during postnatal life. In addition, we show that targeted expression of oncogenic β-catenin in Sox2(+) cells gives rise to pituitary tumors, but, unexpectedly, the tumor mass is not derived from the Sox2(+) mutation-sustaining cells, suggesting a paracrine role of Sox2(+) cells in pituitary oncogenesis. Our data therefore provide in vivo evidence of a role for Sox2(+) stem/progenitor cells in long-term physiological maintenance of the adult pituitary, and highlight an unexpected non-cell-autonomous role for these cells in the induction of pituitary tumors.
authors.affiliation: Birth Defects Research Centre, Neural Development Unit, UCL Institute of Child Health, London, WC1N 1EH, UK. Electronic address: cynthia.andoniadou@kcl.ac.uk.
authors.forename: Cynthia Lilian
authors.initials: CL
authors.lastname: Andoniadou
authors.forename: Danielle
authors.initials: D
authors.lastname: Matsushima
authors.forename: Seyedeh Neda
authors.initials: SN
authors.lastname: Mousavy Gharavy
authors.forename: Massimo
authors.initials: M
authors.lastname: Signore
authors.forename: Albert Ian
authors.initials: AI
authors.lastname: Mackintosh
authors.forename: Marie
authors.initials: M
authors.lastname: Schaeffer
authors.forename: Carles
authors.initials: C
authors.lastname: Gaston-Massuet
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
authors.forename: Thomas Stanley
authors.initials: TS
authors.lastname: Jacques
authors.forename: Paul
authors.initials: P
authors.lastname: Le Tissier
authors.forename: Mehul Tulsidas
authors.initials: MT
authors.lastname: Dattani
authors.forename: Larysa Halyna
authors.initials: LH
authors.lastname: Pevny
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Martinez-Barbera
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006706:Homeostasis; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010902:Pituitary Gland / Q000166:cytology* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse